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IL-13–regulated Macrophage Polarization during Granuloma Formation in an In Vitro Human Sarcoidosis...

IL-13–regulated Macrophage Polarization during Granuloma Formation in an In Vitro Human Sarcoidosis...

https://devfeature-collection.sl.nsw.gov.au/record/TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6348723

IL-13–regulated Macrophage Polarization during Granuloma Formation in an In Vitro Human Sarcoidosis Model

About this item

Full title

IL-13–regulated Macrophage Polarization during Granuloma Formation in an In Vitro Human Sarcoidosis Model

Publisher

United States: American Thoracic Society

Journal title

American journal of respiratory cell and molecular biology, 2019-01, Vol.60 (1), p.84-95

Language

English

Formats

Publication information

Publisher

United States: American Thoracic Society

More information

Scope and Contents

Contents

The mechanisms underlying abnormal granuloma formation in patients with sarcoidosis are complex and remain poorly understood. A novel in vitro human granuloma model was used to determine the molecular mechanisms of granuloma genesis in patients with sarcoidosis in response to putative disease-causing mycobacterial antigens. Peripheral blood mononuclear cells (PBMCs) from patients with active sarcoidosis and from normal, disease-free control subjects were incubated for 7 days with purified protein derivative-coated polystyrene beads. Molecular responses, as reflected by differential expression of genes, extracellular cytokine patterns, and cell surface receptor expression, were analyzed. Unbiased systems biology approaches were used to identify signaling pathways engaged during granuloma formation. Model findings were compared with human lung and mediastinal lymph node gene expression profiles. Compared with identically treated PBMCs of control subjects (n = 5), purified protein derivative-treated sarcoidosis PBMCs (n = 6) were distinguished by the formation of cellular aggregates resembling granulomas. Ingenuity Pathway Analysis of differential expression gene patterns identified molecular pathways that are primarily regulated by IL-13, which promotes alternatively activated (M2) macrophage polarization. M2 polarization was further demonstrated by immunohistochemistry performed on the in vitro sarcoidosis granuloma-like structures. IL-13-regulated gene pathways were confirmed in human sarcoidosis lung and mediastinal lymph node tissues. The in vitro human sarcoidosis granuloma model provides novel insights into early granuloma formation, particularly IL-13 regulation of molecular networks that regulate M2 macrophage polarization. M2 macrophages are predisposed to aggregation and multinucleated giant cell formation, which are characteristic features of sarcoidosis granulomas. Clinical trial registered with www.clinicaltrials.gov (NCT01857401)....

Alternative Titles

Full title

IL-13–regulated Macrophage Polarization during Granuloma Formation in an In Vitro Human Sarcoidosis Model

Identifiers

Primary Identifiers

Record Identifier

TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6348723

Permalink

https://devfeature-collection.sl.nsw.gov.au/record/TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6348723

Other Identifiers

ISSN

1044-1549

E-ISSN

1535-4989

DOI

10.1165/rcmb.2018-0053OC

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